The proposed study is to investigate the effects of HIV in the brain & on neurocognitive functioning as people age. The study incorporates state-of-the-art brain imaging methods along with clinical & laboratory measures of HIV infection. The goal is to achieve greater understanding of factors that influence HIV effects in the brain, & that contribute to changes that occur as HIV-infected patients' age. We will examine how neurocognitive outcome & structural brain changes vary as a function of age & these HIV-associated factors. A longitudinal experimental design will be employed with statistical modeling methods to characterize changes over time. Recent data from our laboratory points to age-associated effects of HIV in the brain, including evidence that older patients (>45 years) have greater deficits at baseline & greater change over time than younger patients. Furthermore, our data suggests that structural brain changes, such as basal ganglia & hippocampal volume loss occur at an accelerated rate in older patients, with brain changes similar to those seen with advanced age. Initial diffusion tensor imagining (DTI) data provides evidence of reduced structural integrity of subcortical systems that appears to evident prior to the development of structural changes on traditional MRI. The proposed study will extend these preliminary findings; comparing young & older (n =120) HIV-infected patients (<> 45 years) with matched cohorts of young & older healthy controls (n=50) over 36-months on neurocognitive, neuroimaging, & laboratory measures. All will undergo laboratory testing including assessment of CD4, viral load, & activated macrophages from plasma & CSF. Structural brain imaging (MPRAGE & FLAIR) & DTI will be acquired at baseline, 12 months, & 36-months, along with the laboratory & neurocognitive measures. The results will inform us about the interaction of HIV infection in the brain & aging over time, will provide metrics for assessing structural brain changes, will extend our knowledge of the clinical application of DTI for brain disorders & may lead to advances in neurodiagnostics for HIV. This study will provide valuable information about the effects of HIV on brain as people age. Knowledge about HIV effects on specific brain structures will be achieved, with new methods developed for assessing these changes. Clinical application of brain imaging methods, most notably in particular MRI diffusion tensor imaging, may occur, which may lead to advanced in diagnostics for HIV effects in the brain. [unreadable] [unreadable] [unreadable]